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• W1965536075 abstract "Abstract We have examined the antisense potency of the hybrid duplexes of fully-matched 3′-, 5′ and interior-chromophore tethered antisense oligos (AON) and three target RNAs (11mer and two 17mers) against RNase H, and found them to be better substrates compared to the native DNA/RNA hybrid. These target RNAs were chosen for complexation with AONs because they have very different folding characteristics as evident from the temperature- and concentration-dependent UV and CD spectroscopy. The differences in the tertiary structures of the target RNAs have been exploited here to investigate the kinetic availability of the single-stranded region accessible for the complexation with the AON during the RNase H promoted cleavage. It has emerged that the cleavage rate of the target RNA in the hybrid is independent of the complexity of the folding of the target RNA, thereby suggesting that (i) The kinetic accessibility of the single strand region in all three RNA targets, ( 11 ), ( 12 ) and ( 13 ), by AONs are very similar, and indeed not rate-limiting, although sequence specificities are non-identical in the 11mer and 17mers RNAs. (ii) The rate of conversion of the folded RNA structures to the single-stranded form, and subsequently its kinetic accessibility to drive the hybrid AON/RNA duplex formation is much faster than the RNase H promoted cleavage rate of the RNA moiety in the hybrid. (iii) This also means that the RNase H promoted cleavage rate of the hybrid is the slowest (i.e. the rate-determining)." @default.
• W1965536075 created "2016-06-24" @default.
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• W1965536075 date "2001-01-01" @default.
• W1965536075 modified "2023-09-27" @default.
• W1965536075 title "The 3′-modified antisense oligos promote faster hydrolysis of the target RNA by RNase H than the natural counterpart" @default.
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• W1965536075 doi "https://doi.org/10.1016/s0040-4020(00)01029-2" @default.
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